This file gives info about transplantation and the immunological problem like tissue rejection. MHC role in transplantation, laws, and types of tissue transplantation. Explains all kinds of tissue rejection and source of tissue. Some immunological terms plus transplantation history, it also includes the genetic basis of Transplantation. Hope it's helpful

1. Transplantation Immunology

2. Transplantation
The process of taking cells, tissues, or
organs from one individual and placing
them into a different individual or
different site of the same individual.
Implantation of “non-self” tissue into
the body
The process of taking cells, tissues, or
organs called a graft (transplant), from
one part or individual and placing them
into another (usually different
individual).

3. Terminologies
Graft: transplanted cells, tissues, or organs.
Donor: the individual who provides the graft.
Recipient: the individual who receives the
graft. Also called the host.
MHC or HLA
Alloantigen and alloantibody

4. History
• 1943:Description of skin graft rejection as an immune process
• 1951:Natural and experimental tolerance
• 1954:First successful clinical kidney transplant between identical
twins
• 1959:Inhibition of antibody production in experiments with
mercaptopurine
• 1960:Prolongation of survival of experimental kidney transplants
by mercaptopurine
• 1961:Prolongation of survival of experimental kidney transplants
by azathioprine
• 1962:Use of azathioprine and steroids in clinical renal transplants
• 1963:First clinical liver transplant

5. Conti……
• 1967:First clinical heart transplant
• 1978:Use of ciclosporin in clinical renal
transplants
• 1981:Use of monoclonal antibodies to
lymphocytes in organ grafting
• 1989:Use of tacrolimus in clinical organ grafts
• 1995:Use of sirolimus in clinical organ grafts
• 1998:Alemtuzumab induction and low-dose
maintenance immunosuppression in clinical renal
transplants

6. GENETIC BASIS OF TRANSPLANTATION
A. Histocompatibility genes and antigens
 Histocompatibility genes encode histocompatibility antigens
 Histocompatibility genes are co-dominantly expressed
 The MHC of humans is termed HLA
 Is located on short arm of chromosome 6
 It includes 3 regions: class Ia (loci A, B, C) class Ib (loci E, F, G, H),
class II (loci DR, DQ, DP) and class III
 Genes of class Ia and class II are highly polymorphic, while those of
class Ib and class III are not
 Polymorphism means occurrence of several alleles i.e. genes
encoding various MHC antigens located at the same locus

7. • Histocompatibility antigens are expressed
on all nucleated cells (class I) and on APC, B
cells, monocytes/macrophages (class II)
• They are targets for rejection
• They are inherited from both parents as
MHC haplotypes and are co-dominantly
expressed
• Non-MHC or minor MHCs

8. B. Types of grafts
Classification of grafts by donor-
recipient genetic relationship.
• Auto-graft
• Syngeneic graft
• Allograft
• Xeno-graft

9. C. The laws of transplantation
“A host can recognize as foreign and mount a
response against any histocompatibility antigen
not encoded within its own cells”
Inbreeding
Inbred strains
Congenic strains

10. TISSUE REJECTION
Transplant rejection occurs when transplanted
tissue is rejected by the recipient's immune
system, which destroys the transplanted
tissue.
T cells can detect and be activated against
histocompatibility antigens through two
different pathways of recognition
Direct recognition
Indirect recognition

11. Direct Alloantigen recognition
• T cell recognized
unprocessed
allogeneic MHC
molecules on graft
APCs
• A professional APC
for MHC class II or
any allogeneic cell
for MHC class

12. Indirect recognition
• Presentation
of processed
peptide of
allogeneic
MHC
molecules
bound to self
MHC
molecules

14. The Immune response to Liver
Graft

15. A. Types of rejection and Immune
responses involved in rejection
Rejection responses fall into three general
categories
Chronic rejection
Acute rejections
Hyper-acute rejections

16. Hyper-acute rejection
• Occurs within 24 hours of transplant
• If the host serum has pre-existing
antibodies against the graft antigens the
transplant is quickly rejected even before
vascularization.
• ABO blood Antigens
• Antibody-Dependent Cell-Mediated
Cytotoxicity: Type II Hypersensitivity
Reaction

18. Type II Hypersensitivity Reaction
• In Hypersensitivity reaction body can respond
to its own body components that are usually
ignored.
• Antibodies mediated immune reactions
1. Complement mediated reactions
2. Complement independent reactions

21. A. Neutrophil Cytotoxicity
Neutrophil
Complement
proteins
FCRs
Chemotactic of
Neutrophil

22. Releases radical
Oxygen species
Causes cellular damage and
Inflammation leads to cell death

23. B. Opsonization and Phagocytosis
Macrophages
FCRs

24. Binding Engulfing and breaking

25. C. Membrane Attack Complex (MAC)
formation
MAC Formation Efflux of extra cellular fluid
Extra-
cellular
space

26. Cell swelling Cell Lysis

27. D. Apoptotic Response
Bound IgG or IgM Antibody can be recognized by NK Cells

29. E. Disruption of Cell Function
1. Blocks receptor to stops
Signal transmission
2. Antibody binds to receptor Activating it
and act as transmitter to send wrong signals

30. Acute rejections
• Begins in first few weeks after transplantation
• T-Cell mediated Immune response
• Type IV hypersensitivity response also called
as DTH
• Direct pathway of allorecognition
• Activation of T-cell via antigen leads to the
initiation of various immune cells

32. Chronic rejection
• Take months to years to happen ( slow
rejection)
• Indirect allorecognition
• T-Cell mediated immune response
• Hypersensitivity type III & IV
• Blood vessel damage, thickening, ischemia
and organ death

34. Type III Hypersensitivity
• Immune Complex mediated
• CausedGenerated by soluble immune
Complex of antibody and antigen
• Complexes can be larger which usually
removed macrophages but smaller can remain
in circulations
• Smaller complex can activate the cascade of
reactions by activating other immune cells

37. B. Therapeutic intervention
• The initial effort to minimize the risk of rejection is to
genetically match the donor and recipient as closely as
possible. However, some degree of mismatch is present in
most transplants.
• The next step that can be taken is to inhibit the ability of the
recipient immune system to attack and damage the
engrafted tissues. This inhibition is approached in two
general ways:
• Specific immune tolerance: It involves a selective inhibiting
of the responsiveness to a given antigen or set of antigens.
• Immune suppression (or immunosuppression): It involves
inhibiting general immune responsiveness without regard to
the specificity.

38. TISSUE-SPECIFIC CONSIDERATIONS
Special problems may arise when particular
tissues are transplanted.
We will discuss two of these situations, those
involving:
• Blood transfusions
• The transfer of bone marrow

39. A. Transfusion
ABO: The ABO antigen system is a set of
carbohydrate structures on erythrocyte surfaces
and on some endothelial and epithelial cells. They
are synthesized by glycosyl transferases encoded
by two loci: the H locus and the ABO locus.
Rh: The Rh ("Rhesus") antigens on erythrocyte
surfaces are proteins. When an Rh-negative (Rh-)
individual is exposed to Rh positive (Rh+)
erythrocytes, he or she can generate antibodies,
some of which are of the lgG isotype

40. B. Bone marrow
• The bone marrow carries stem cells for the
entire hematopoietic system and (at least
hypothetically) could be used to treat
individuals in whom some or all of these
tissues are intrinsically defective or may have
been damaged
• Graft-versus-host (GVH) response, and the
resulting damage is Graft-versus-host disease
(GVHD

41. C. Immune-privileged sites
Some anatomic sites are "permissive" in
tolerating genetic mismatches between donor
and recipient that would lead to prompt
rejection in most parts of the body.
• The eye
• The lumen of the testes
• The brain
• The placenta

42. TISSUE SOURCES
• Two types of sources
1. Human tissues and organs
2. Nonhuman (Xeno-) tissues and organs

43. A. Human tissues and organs
Organ procurement and distribution
Stem cell and fetal sources
Ethical considerations

44. B. Nonhuman (xeno-) tissues and
organs
 The shortage of available human organs has spurred
research into the use of nonhuman alternatives. Numerous
attempts have been made to use animal donors.
 Primates are an obvious donor choice because of their
close genetic relationship to humans.
 Pigs have many physiologic similarities to humans, and
some breeds have organs that are an appropriate size for
use in human recipients.
 Pig skin has also been used on occasion for temporary
coverage of damaged areas in human burn victims.
 Xenotransplantation has not been very successful or widely
used.

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